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1.
Cell Commun Signal ; 22(1): 136, 2024 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374141

RESUMEN

Diabetic kidney disease (DKD) is a long-term and serious complication of diabetes that affects millions of people worldwide. It is characterized by proteinuria, glomerular damage, and renal fibrosis, leading to end-stage renal disease, and the pathogenesis is complex and involves multiple cellular and molecular mechanisms. Among three kinds of intraglomerular cells including podocytes, glomerular endothelial cells (GECs) and mesangial cells (MCs), the alterations in one cell type can produce changes in the others. The cell-to-cell crosstalk plays a crucial role in maintaining the glomerular filtration barrier (GFB) and homeostasis. In this review, we summarized the recent advances in understanding the pathological changes and interactions of these three types of cells in DKD and then focused on the signaling pathways and factors that mediate the crosstalk, such as angiopoietins, vascular endothelial growth factors, transforming growth factor-ß, Krüppel-like factors, retinoic acid receptor response protein 1 and exosomes, etc. Furthermore, we also simply introduce the application of the latest technologies in studying cell interactions within glomerular cells and new promising mediators for cell crosstalk in DKD. In conclusion, this review provides a comprehensive and updated overview of the glomerular crosstalk in DKD and highlights its importance for the development of novel intervention approaches.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Podocitos , Humanos , Podocitos/patología , Nefropatías Diabéticas/metabolismo , Células Mesangiales/metabolismo , Células Endoteliales/metabolismo , Glomérulos Renales/patología , Diabetes Mellitus/patología
2.
ACS Appl Mater Interfaces ; 15(38): 44742-44751, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37721982

RESUMEN

Exploring new ways to reconstruct the structure and function of inappropriate organic fluorophores for improving amyloid-ß (Aß) fluorescent imaging performance is desired for precise detection and early diagnosis of Alzheimer's disease (AD). With stilbazolium dyes as examples, here, we present a multipronged approach to comprehensively improved the Aß fluorescent imaging performance through a flexible bivalent method, where a flexible carbon chain was introduced to link two monomers to form a homodimer. Our results reveal a mechanism wherein the flexible linker creates a well-defined probe with specific orientations and distinct photophysical properties. Applying this approach in combination with theoretical simulation, the homodimers exhibited a comprehensive improvement of the Aß fluorescent imaging performance of the dye monomers, including better photostability and higher signal-to-noise (S/N) ratio, higher "off-on" near-infrared fluorescence (NIRF) response sensitivity, higher specificity and affinity to Aß deposits, and more reasonable lipophilicity for blood-brain barrier (BBB) penetrability. The results demonstrate that flexible homodimers offer a multipronged approach to obtaining high-performance NIRF imaging reagents for the detection of Aß deposits both in vitro and in vivo.


Asunto(s)
Enfermedad de Alzheimer , Colorantes Fluorescentes , Humanos , Péptidos beta-Amiloides , Enfermedad de Alzheimer/diagnóstico por imagen , Barrera Hematoencefálica , Carbono
3.
Phytomedicine ; 114: 154763, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37001295

RESUMEN

BACKGROUND: Membranous nephropathy (MN) is one of the cardinal causes of nephrotic syndrome in adults, but an adequate treatment regimen is lacking. PURPOSE: We assessed the effect of Moshen granule (MSG) on patients with MN and cationic bovine serum albumin (CBSA)-induced rats. We further identified the bioactive components of MSG and revealed the underlying molecular mechanism of its renoprotective effects. METHODS: We determined the effect of MSG on patients with MN and CBSA-induced rats and its components on podocyte injury in zymosan-activated serum (ZAS)-elicited podocytes and revealed their regulatory mechanism on the Wnt/ß-catenin/renin-angiotensin system (RAS) signalling axis. RESULTS: MSG treatment improved renal function and reduced proteinuria in MN patients and significantly reduced proteinuria and preserved the protein expression of podocin, nephrin, podocalyxin and synaptopodin in CBSA-induced MN rats. Mechanistically, MSG treatment significantly inhibited the protein expression of angiotensinogen, angiotensin converting enzyme and angiotensin II type 1 receptor, which was accompanied by inhibition of the protein expression of Wnt1 and ß-catenin and its downstream gene products, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in CBSA-induced MN rats. We further identified 81 compounds, including astragaloside IV (AGS), calycosin, barleriside A and geniposidic acid, that preserve the podocyte-specific protein expression in ZAS-induced podocytes. Among these four compounds, AGS exhibited the strongest inhibitory effects on podocyte protein expression. AGS treatment significantly inhibited the protein expression of RAS components and Wnt1 and ß-catenin and its downstream gene products in ZAS-induced podocytes. In contrast, the inhibitory effect of AGS on podocyte-specific proteins, ß-catenin downstream gene products and RAS components was partially abolished in ZAS-induced podocytes treated with ICG-001 and ß-catenin siRNA. CONCLUSION: This study first demonstrates that AGS mitigates podocyte injury by inhibiting the activation of RAS signalling via the Wnt1/ß-catenin pathway by both pharmacological and genetic methods. Therefore, AGS might be considered a new ß-catenin inhibitor that inhibits the Wnt1/ß-catenin pathway to retard MN in patients.


Asunto(s)
Glomerulonefritis Membranosa , Sistema Renina-Angiotensina , Ratas , Animales , beta Catenina/metabolismo , Proteinuria , Vía de Señalización Wnt
4.
Front Pharmacol ; 13: 840560, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35721109

RESUMEN

Background: There exists no broad agreement of experts on the practice of pharmaceutical care for cancer pain management in outpatient clinics. Objectives: This study aimed to use the Delphi consensus process to provide expert recommendations on the practice of cancer pain management in outpatient clinics from the point of view of pharmaceutical care in clinical practice and future clinical trials. Methods: A comprehensive literature review was conducted to draft the initial practice. In this process, 30-40 senior experts from various provinces in China were invited to rank the items of practice during the two Delphi consultations. The definitions of consensus included a combination with an average score of ≥4, the percentage of experts rating the scores at >4 points, and the coefficient of variation of the scores. Results: The expert panel comprised 18 pharmacists, 3 anesthesiologists, 6 oncologists, and 9 nurses. As a result of a comprehensive review, 33 items were initially formed. Among them, the consensus was reached for 27 items after the first Delphi round. The other six items and a total of five items for supplementation entered the second round, among which consensus was reached for eight items and three items were excluded. Expert consensus was achieved on 35 items after two rounds of consultation, which involved the collection of patient basic information, comprehensive pain assessment, breakthrough or neuropathic pain assessment, analgesic treatment evaluation, out-of-hospital follow-up, medical records, and evidence-based documents for reference. Conclusion: The final list of 35 items could be used to develop the practice of pharmaceutical care for cancer pain management in outpatient clinics in China. The practice may aid in the standardization of pharmaceutical care for pain, relieve pain to the greatest extent possible, and enhance the level of pain management in China.

5.
Aging Dis ; 13(3): 732-752, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35656117

RESUMEN

Fibrosis is a pathological manifestation of wound healing that replaces dead/damaged tissue with collagen-rich scar tissue to maintain homeostasis, and complications from fibrosis contribute to nearly half of all deaths in the industrialized world. Ageing is closely associated with a progressive decline in organ function, and the prevalence of tissue fibrosis dramatically increases with age. Despite the heavy clinical and economic burden of organ fibrosis as the population ages, to date, there is a paucity of therapeutic strategies that are specifically designed to slow fibrosis. Aryl hydrocarbon receptor (AhR) is an environment-sensing transcription factor that exacerbates aging phenotypes in different tissues that has been brought back into the spotlight again with economic development since AhR could interact with persistent organic pollutants derived from incomplete waste combustion. In addition, gut microbiota dysbiosis plays a pivotal role in the pathogenesis of numerous diseases, and microbiota-associated tryptophan metabolites are dedicated contributors to fibrogenesis by acting as AhR ligands. Therefore, a better understanding of the effects of tryptophan metabolites on fibrosis modulation through AhR may facilitate the exploitation of new therapeutic avenues for patients with organ fibrosis. In this review, we primarily focus on how tryptophan-derived metabolites are involved in renal fibrosis, idiopathic pulmonary fibrosis, hepatic fibrosis and cardiac fibrosis. Moreover, a series of ongoing clinical trials are highlighted.

6.
J Mater Chem B ; 10(25): 4832-4839, 2022 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-35674394

RESUMEN

Photothermal therapy (PTT) is an emerging paradigm for the degradation of amyloid-ß (Aß) aggregations and has become an effective way of treating Alzheimer's disease (AD). A promising PTT therapeutic option requires control of at least two key functional aspects: controllable photoactivity and specific activation. In this work, a near-infrared (NIR)-activated thermo-switchable biopolymeric PTT agent was designed and synthesized by conjugating a molecular rotor-based boron dipyrromethene photosensitizer (BDP) to a temperature-responsive polymer backbone of biopolymeric hydroxypropyl cellulose (HPC). The as-synthesized BDP-HPC exhibited an ultra-high PCE of 78.1% along with prominent cycling stability of phase-transition behavior under NIR irradiation in the light of the lower critical solution temperature (LCST at 42.5 °C). Importantly, the NIR irradiation can manipulate the reversible phase transition behavior of the resultant BDP-HPC that reveals high effectiveness in inhibiting Aß aggregation together with the obvious ability to dissociate Aß aggregations. Our work reveals an accurate modulation strategy for versatile and high-performance AD treatment.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Humanos , Rayos Infrarrojos , Fármacos Fotosensibilizantes/farmacología , Fototerapia , Polímeros/farmacología
7.
Chem Sci ; 13(20): 5902-5912, 2022 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-35685783

RESUMEN

The development and exploration of new nanostructural inhibitors against Alzheimer's disease (AD)-associated amyloid-ß (Aß) fibrillation have attracted extensive attention and become a new frontier in nanomedicine. However, focusing on finding an effective nanostructure is one of the most challenging parts of the therapeutics task. Herein, nanoscale spherical covalent organic frameworks (COFs) via post-synthetic functionalization with sodium phosphate (SP) groups on the channel networks were found to efficiently inhibit Aß fibrillation. The as-prepared uniform SP-COF nanospheres with high surface area, good crystallinity, and chemical stability were characterized by multifarious microscopic and spectroscopic techniques. Moreover, molecular dynamics simulation together with fibrillation kinetics and cytotoxicity assay experiments shows that there were restricted-access adsorption channels in the SP-COFs which were formed by the cavities with size and functional groups accommodated to the Aß peptide sequence and significantly affected the fibrillation and cytotoxicity of Aß. Transmission electron microscopy (TEM), dynamic light scattering (DLS) monitoring, isothermal titration calorimetry (ITC), Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra measurements, and confocal imaging observation were performed to understand the inhibition mechanism and influencing factors of the SP-COFs. To our knowledge, our strategy is the first exploration of COF-based anti-amyloidogenic nanomaterials with high affinity and specific targeting, which are crucial for the inhibition of Aß fibrillation for AD prevention and treatment.

8.
Anim Genet ; 53(5): 700-705, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35748186

RESUMEN

In domestic goats, wattles often appear in even numbers, mostly on the neck and a few under the ear. Goat wattle is composed of ectopic cartilage tissue covered by skin and was reported as a dominant inheritance. Thirty-eight goats from two Southwest Chinese breeds were studied to elucidate the genetic basis of wattle phenotype in goat. Their genomes were sequenced for wide-genome selective sweep analysis (WGSA) and a genome-wide association study (GWAS). The WGSA results revealed 500 candidate genes identified by fixation index and π ratio and 261 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched with 195 genes and 38 significantly enriched KEGG items. In particular, three chondrogenesis-related pathways (Wnt, Hippo and MAPK signaling pathways) were found. Among the 500 genes, 474 were enriched to 2855 Gene Ontology items, and four (BMP2, BMP4, RARA and MSX1) were annotated in the regulation and development of chondrogenesis. Four chondrogenesis-related genes (GREM1, NEDD4, ATG7 and ITGA1) were identified from 519 single-nucleotide polymorphisms (SNPs) with a GWAS above the threshold. Six and 11 SNPs on chromosome 10 are located on GREM1 and NEDD4 respectively, and the highest numbers of SNPs on chromosomes 20 and 22 are located on ITGA1 and ATG7 respectively. All of these genes are related to cartilage development. This study identified a series of genes related to chondroplasia by GWAS and WGSA and presented the possibility that wattle inheritance may be influenced by multiple genes. This work provides a new theoretical understanding of the hereditary basis of wattle phenotype.


Asunto(s)
Estudio de Asociación del Genoma Completo , Cabras , Animales , Cresta y Barbas , Genoma , Estudio de Asociación del Genoma Completo/veterinaria , Cabras/genética , Fenotipo , Polimorfismo de Nucleótido Simple
9.
ACS Appl Bio Mater ; 5(3): 1210-1221, 2022 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-35191674

RESUMEN

Covalent organic framework nanospheres (COF NSs) have garnered special attention due to their uniform sphere morphology, adjustable particle size, and mesoporous microenvironment. However, methods to control an optimal particle size scale while achieving solution dispersibility and specific surface properties remain underdeveloped, which precludes many of the biomedical applications. Here, we propose and develop a general strategy to access simultaneous size control and surface functionalization of uniform spherical COF NSs in a single step using aspartic acid (d-/l-Asp) that plays center roles in an acid catalyst, hydrophilicity, size-controllable synthesis, and chiral enantiomer. In this study, for the first time, we have employed a surface chemistry engineering study to create a variety of nanoscale spherical COFs and subsequently measure parameters to evaluate the effectiveness of Asp in the regulation of the particle size. Moreover, the potential utilization of the d/l-enantiomeric Asp-COF NSs in preventing ß-amyloid (Aß) aggregation is investigated by analyzing their interactions with Aß amyloids using a multitechnique experimental approach. To our knowledge, our strategy is the first synthesis of hydrophilic COF NSs with an optimal length scale and a chiral-selective targeting surface, which are crucial for the inhibition of Aß fibrillation for Alzheimer's disease prevention.


Asunto(s)
Estructuras Metalorgánicas , Péptidos beta-Amiloides , Ácido Aspártico , Estructuras Metalorgánicas/química , Tamaño de la Partícula , Propiedades de Superficie
10.
ACS Chem Neurosci ; 12(22): 4236-4248, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34724384

RESUMEN

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an imbalance between the production and clearance of amyloid-ß (Aß) species. AD not only influences the life quality of the patients but also heavily burdens the families and society. Therefore, it is an urgent mission to research and develop some new anti-amyloid aggregation drugs. In recent years, there were research and development of engineered nanostructures as Aß amyloid inhibitors have attracted extensive attention and become a new frontier in nanomedicine. The effects of nanostructural surface properties (e.g., morphology, charge, hydrophobicity) on inhibition of Aß aggregation are modulated by adsorbed Aß peptides. Nevertheless, chirality has been seldom considered in recognition of Aß species and modulation of Aß aggregations. Moreover, a more relevant question for chiral inhibitors is little known about the molecular mechanism of how to interface chiral effects Aß targeting recognition and effective mitigation of amyloidosis at the molecular level. Herein, we review recent experimental and theoretical results acquired in the specific areas of artificial chiral nanostructure inhibitors. This article will be essential to provide a microlevel insight into the effects of chiral nanointerfaces on amyloidosis processes as well as the development of chiral inhibitor drugs against Aß fibrillation.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Enfermedad de Alzheimer/tratamiento farmacológico , Amiloide , Humanos
11.
ACS Appl Mater Interfaces ; 13(48): 56812-56824, 2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34817983

RESUMEN

The protein corona on nanoparticles (NPs) is a critical problem that often screens the targeting molecules and becomes one of the key reasons for the lack of practical application in nanotherapy. It is critical to fully understand the mechanism of the nanoparticle-biological interactions to design the nanoparticle-based therapeutic agents. Some types of proteins can be precoated on the nanoparticles to avoid unwanted protein attachment; however, the ultralow level of protein corona is hard to achieve, and the relationship of the antifouling property of the precoated protein nanoparticles with protein conformation and protein-nanoparticle interaction energy has never been investigated. In this work, we provided the quantitative protein corona composition analysis on different precoated protein nanoparticles, and on the basis of the molecular simulation process, we found their antifouling property strongly depended on the interaction energy of the precoated protein-serum protein pair and the number of hydrogen bonds formed between them. Furthermore, it also depended on the nanoparticle-serum protein pair interaction energy and the protein conformation on the nanoparticle. The casein coated nanoparticle with the antifouling property was determined, and after aptamer conjugation and drug loading, they exhibited superior targeting and internalization behavior for photodynamic and photothermal therapy in vitro and in vivo. Our work adds to the understanding of the protein corona behavior of precoated protein nanoparticles, and the determined antifouling NP can potentially be used as a highly efficient nanodrug carrier.


Asunto(s)
Materiales Biomiméticos/química , Nanopartículas/química , Corona de Proteínas/análisis , Ensayo de Materiales , Simulación de Dinámica Molecular , Tamaño de la Partícula
12.
Front Pharmacol ; 12: 741801, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34621173

RESUMEN

Background: Hirudin has been widely used in the treatment of antifibrosis. Previous studies have shown that hirudin can effectively improve the clinical remission rate of chronic kidney disease. However, the mechanism of its renal protection has not been systematically investigated. Methods: In this study, the reliability of UUO-induced renal interstitial fibrosis was evaluated by histopathological verification. High-throughput transcriptome sequencing was used to elucidate the molecular mechanism of hirudin, differentially expressed mRNAs were identified, and their functions were analyzed by GO analysis and GSEA. In addition, the RNA-seq results were validated by in vitro and vivo experiments. Results: We found 322 identical differential expressed genes (IDEs) in the UUO hirudin-treated group compared with the sham group. Functional enrichment analysis indicated that cellular amino acid metabolic processes were the most obvious enrichment pathways in biological processes. In terms of molecular functional enrichment analysis, IDEs were mainly enriched in coenzyme binding, pyridoxal phosphate binding and other pathways. In addition, microbody is the most obvious pathway for cellular components. A total of 115 signaling pathways were enriched, and AMPK, JAK-STAT, and PI3K-Akt signaling pathways were the important signaling pathways enriched. We found that PI3K, p-Akt, and mTOR expression were significantly reduced by hirudin treatment. In particular, our results showed that hirudin could induce a decrease in the expression of autophagy-related proteins such as P62, LC3, Beclin-1 in TGF-ß1-induced NRK-52E cells. Conclusion: Our results suggest that hirudin may protect the kidney by ameliorating renal autophagy impairment through modulating the PI3K/Akt pathway.

14.
JMIR Mhealth Uhealth ; 9(8): e24555, 2021 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-34398796

RESUMEN

BACKGROUND: Self-management of ambulatory cancer pain is full of challenges. Motivated by the need for better pain management, we developed a WeChat-supported platform, Medication Housekeeper (MediHK), to enhance communication, optimize outcomes, and promote self-management in the home setting. OBJECTIVE: We conducted a randomized controlled trial to assess whether the joint physician-pharmacist team through MediHK would provide better self-management of ambulatory patients with cancer pain. METHODS: Patients were randomly assigned to either an intervention group or control group. During the 4-week study period, the pharmacist would send 24-hour pain diaries daily, adverse drug reaction (ADR) forms every 3 days, and the Brief Pain Inventory form every 15 days to patients in the intervention group via MediHK. If a patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician, who was then responsible for prescribing or adjusting pain medications. If no adjustments were needed, the pharmacist provided appropriate targeted education based on knowledge deficits. Patients in the control group received conventional care and did not receive reminders to fill out the forms. However, if the control group patients filled out a form via MediHK, the pain management team would review and respond in the same way as for the intervention group. The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included patient-reported outcome measures, medication adherence, ADRs, and rehospitalization rates. RESULTS: A total of 100 patients were included, with 51 (51%) in the intervention group and 49 (49%) in the control group. The worst pain scores, least pain scores, and average pain scores in the intervention group and the control group were statistically different, with median values of 4 (IQR 3-7) vs 7 (IQR 6-8; P=.001), 1 (IQR 0-2) vs 2 (IQR 1-3; P=.02), and 2 (IQR 2-4) vs 4 (IQR 3-5; P=.001), respectively, at the end of the study. The pain interference on patients' general activity, mood, relationships with others, and interests was reduced, but the difference was not statistically significant compared with the control group (Ps=.10-.76). The medication adherence rate increased from 43% to 63% in the intervention group, compared with an increase of 33% to 51% in the control group (P<.001). The overall number of ADRs increased at 4 weeks, and more ADRs were monitored in the intervention group (P=.003). Rehospitalization rates were similar between the 2 groups. CONCLUSIONS: The joint physician-pharmacist team operating through MediHK improved pain management. This study supports the feasibility of integrating the internet into the self-management of cancer pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900023075; https://www.chictr.org.cn/showproj.aspx?proj=36901.


Asunto(s)
Dolor en Cáncer , Neoplasias , Médicos , Instituciones de Atención Ambulatoria , Dolor en Cáncer/tratamiento farmacológico , Humanos , Cumplimiento de la Medicación , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Farmacéuticos , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
Jpn J Clin Oncol ; 51(6): 932-941, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-33521814

RESUMEN

OBJECTIVE: Comparing the characteristics of end-of-dose failure patients and non-end-of-dose failure patients in the Chinese population and exploring the factors that may affect the occurrence of end-of-dose failure in cancer pain patients. METHODS: The outpatient with cancer pain from 2016 to 2019 were collected through hospital information system, and patients were included who met the following criteria: patients with the average numerical rating scale  ≥4 points within 3 days after taking the oxycodone sustained-release preparation, titrated to an effective therapeutic dose suitable for patients, had at least two clinical visits information of the patient with a minimum of ≥3 days between visits, the average numerical rating scale of the next visit after the treatment of occasional pain is ≥4, and were divided into end-of-dose failure group and non-end-of-dose failure group. RESULTS: Age (P < 0.05, odds ratio 0.933), diagnosis of nasopharyngeal carcinoma (P < 0.05, odds ratio 0.009), pain site is the head and neck (P < 0.05, odds ratio 0.005) and the abdomen (P < 0.01, odds ratio 0.021), and the metastatic site is the liver (P < 0.05, odds ratio 0.001) are related to the occurrence of end-of-dose failure. CONCLUSIONS: Younger patients are more likely to develop end-of-dose failure. Patients diagnosed with nasopharyngeal cancer, with pain in the head and neck and abdomen, and with liver metastases have a lower incidence of end-of-dose failure.


Asunto(s)
Dolor en Cáncer/tratamiento farmacológico , Preparaciones de Acción Retardada/uso terapéutico , Oxicodona/uso terapéutico , Comprimidos/uso terapéutico , Administración Oral , Estudios de Casos y Controles , Preparaciones de Acción Retardada/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxicodona/farmacología , Estudios Retrospectivos , Comprimidos/farmacología
16.
Xenobiotica ; 51(5): 616-623, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33509019

RESUMEN

1. Breviscapine was an active ingredient of flavonoid glycosides. Our present study was conducted to evaluate the impact of breviscapine on the pharmacokinetics of losartan and its active metabolite E-3174, and that relationship with the gene polymorphism of CYP2C9 in healthy Chinese volunteers, to provide a basis for clinical rational drug use.2. The genotypes of 217 healthy Chinese subjects were determined using PCR-RFLP. Twelve healthy subjects were selected and were known CYP2C9 genotypes (six CYP2C9*1/*3 and six CYP2C9*1/*1) in a two-phase randomised crossover design study. These subjects were given daily doses of 120 mg (40 mg, three times a day) of breviscapine or a placebo for 14 days, followed by 50 mg losartan on day 15.3. Compared with individuals carrying the CYP2C9*1/*1 genotype, the CYP2C9*1/*3 genotype showed an increase in the AUC(0-36) (833.6 ± 379.8 ng h ml-1 vs. 526.1 ± 140.1 ng h ml-1, p < 0.05) and a decrease in the MR (the metabolic ratio of losartan, AUCE-3174/AUClosartan) (2.67 ± 1.40 vs. 4.56 ± 0.83, p < 0.05) of losartan during the placebo treatment phase. Individuals with genotype CYP2C9*1/*3 showed a significant increase in AUC(0-36) (2335 ± 851.8 ng h ml-1 vs. 1927 ± 949.5 ng h ml-1, p < 0.05) and AUC(0-∞) (2363 ± 875.6 ng h ml-1 vs. 1966 ± 966.1 ng h ml-1, p < 0.05) of E-3174 after breviscapine treatment compared to the placebo group.4. In healthy subjects, breviscapine had no significant effect on the pharmacokinetics of losartan. The activity of CYP2C9 enzyme to losartan metabolism was more significant in subjects with CYP2C9*1/*3 than those with CYP2C9*1/*1 genotype.


Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Losartán , Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP2C9/genética , Flavonoides , Genotipo , Voluntarios Sanos , Humanos , Polimorfismo Genético
17.
Nanoscale ; 11(16): 7885-7892, 2019 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-30964496

RESUMEN

Nanoscale carbon dots (CDs) have drawn increasing attention in photoelectrochemical (PEC) sensors for biotoxin detection owing to their many merits including excellent optical, electric and photoelectric properties. In this work, a novel strategy is proposed to improve the photoelectrical response performance of CDs by taking advantage of the synergistic effect of nitrogen and sulfur co-doping and copper phthalocyanine non-covalent functionalization approaches, which rightly adjusts the energy level of CDs, optimization of intimate interfacial contact, extension of the light absorption range, and enhancement of charge-transfer efficiency. This work demonstrates that heteroatom doping and chemical functionalization can endow CDs with various new and improved physicochemical, optical, and structural performances. This synergy contributes enormously to the molecular imprinting photoelectrochemical (MIP-PEC) sensor for toxin detection, and the work typically provided a wide linear range of 0.01 to 1000 ng mL-1 with a detection limit of 0.51 pg mL-1 for ochratoxin A (OTA).

18.
Ecol Evol ; 8(10): 5111-5123, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29876086

RESUMEN

The objective of this study was to assess the genetic diversity and population structure of goats in the Yangtze River region using microsatellite and mtDNA to better understand the current status of those goat genetic diversity and the effects of natural landscape in fashion of domestic animal genetic diversity. The genetic variability of 16 goat populations in the littoral zone of the Yangtze River was estimated using 21 autosomal microsatellites, which revealed high diversity and genetic population clustering with a dispersed geographical distribution. A phylogenetic analysis of the mitochondrial D-loop region (482 bp) was conducted in 494 goats from the Yangtze River region. In total, 117 SNPs were reconstructed, and 173 haplotypes were identified, 94.5% of which belonged to lineages A and B. Lineages C, D, and G had lower frequencies (5.2%), and lineage F haplotypes were undetected. Several high-frequency haplotypes were shared by different ecogeographically distributed populations, and the close phylogenetic relationships among certain low-frequency haplotypes indicated the historical exchange of genetic material among these populations. In particular, the lineage G haplotype suggests that some west Asian goat genetic material may have been transferred to China via Muslim migration.

19.
Chem Asian J ; 13(11): 1415-1418, 2018 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-29582560

RESUMEN

A CoII coordination polymer built from a mixed azide and zwitterionic pyridinium ions and its temperature-dependent magnetic properties are described. We used the Markov chain Monte Carlo (MCMC) method to fit the data, and found the following results: (1) there are strong correlations between the model parameters; (2) the data at above 28 K are well fitted by the magnetism model.

20.
Medicine (Baltimore) ; 97(13): e0137, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29595638

RESUMEN

This study aimed to compare the efficacy of thromboelastography (TEG) and conventional coagulation methods in predicting hemorrhage risk in patients with leukemia.A total of 226 patients diagnosed with leukemia were included and divided into bleeding and nonbleeding groups. All patients had their blood samples taken for TEG test to measure the reaction time (R time), alpha (α angle), and maximum amplitude (MA) as well as measure platelet count (PLT), prothrombin time, and activated partial thromboplastin time. Patients were followed up for bleeding episodes.The multivariate analysis showed that PLT [odds ratio (OR) = 0.993] and MA (OR = 0.921) have better association with bleeding risk. Receiver operating characteristic (ROC) analysis showed that the combination of PLT and MA (AUC = 0.824) was better for hemorrhage risk prediction than PLT [area under the curve (AUC) = 0.730] and MA (AUC = 0.819) alone.The combination of TEG and conventional coagulation methods could help in assessing the risk of hemorrhage in patients with leukemia.


Asunto(s)
Hemorragia/diagnóstico , Hemorragia/etiología , Leucemia/sangre , Leucemia/complicaciones , Tromboelastografía , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Leucemia/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Adulto Joven
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