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1.
BMC Genomics ; 25(1): 266, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461245

RESUMEN

BACKGROUND: DNA storage has the advantages of large capacity, long-term stability, and low power consumption relative to other storage mediums, making it a promising new storage medium for multimedia information such as images. However, DNA storage has a low coding density and weak error correction ability. RESULTS: To achieve more efficient DNA storage image reconstruction, we propose DNA-QLC (QRes-VAE and Levenshtein code (LC)), which uses the quantized ResNet VAE (QRes-VAE) model and LC for image compression and DNA sequence error correction, thus improving both the coding density and error correction ability. Experimental results show that the DNA-QLC encoding method can not only obtain DNA sequences that meet the combinatorial constraints, but also have a net information density that is 2.4 times higher than DNA Fountain. Furthermore, at a higher error rate (2%), DNA-QLC achieved image reconstruction with an SSIM value of 0.917. CONCLUSIONS: The results indicate that the DNA-QLC encoding scheme guarantees the efficiency and reliability of the DNA storage system and improves the application potential of DNA storage for multimedia information such as images.


Asunto(s)
Algoritmos , Compresión de Datos , Reproducibilidad de los Resultados , ADN/genética , Compresión de Datos/métodos , Procesamiento de Imagen Asistido por Computador/métodos
2.
Anal Chem ; 96(5): 2008-2021, 2024 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-38276876

RESUMEN

Nontargeted lipidomics using liquid chromatography-tandem mass spectrometry can detect thousands of molecules in biological samples. However, the annotation of unknown oxidized lipids is limited to the structures present in libraries, restricting the analysis and interpretation of experimental data. Here, we describe Doxlipid, a computational tool for oxidized lipid annotation that predicts a dynamic MS/MS library for every experiment. Doxlipid integrates three key simulation algorithms to predict libraries and covers 32 subclasses of oxidized lipids from the three main classes. In the evaluation, Doxlipid achieves very high prediction and characterization performance and outperforms the current oxidized lipid annotation methods. Doxlipid, combined with a molecular network, further annotates unknown chemical analogs in the same reaction or pathway. We demonstrate the broad utility of Doxlipid by analyzing oxidized lipids in ferroptosis hepatocellular carcinoma, tissue samples, and other biological samples, substantially advancing the discovery of biological pathways at the trace oxidized lipid level.


Asunto(s)
Lípidos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Lípidos/análisis , Cromatografía Liquida/métodos , Algoritmos , Simulación por Computador
3.
Chemistry ; 30(3): e202302893, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-37867144

RESUMEN

Two new pentagon-embedded carbo[11]helicenes have been designed and synthesized in a three-step process, which are the first example of carbo[11]helicenes through the post-functionalization of twistacene. TD-DFT analyses indicate that both of them possess high enantiomerization barriers of 42.29 kcal/mol and 40.76 kcal/mol, respectively. They emit strong red fluorescence and can be chemically oxidized into stable cationic radicals upon addition of AgSbF6 evidenced by the bathochromic-shifted absorption spectra and the appearance of electronic paramagnetic resonance (EPR) signals. In addition, such helical derivatives can be chosen as radiative cooling materials in a glass model house, and the maxima of 5.4 °C for the former and 6.5 °C for the latter are found in the comparative tests, which might be caused by the NIR reflective response.

4.
Chemistry ; 30(34): e202400740, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38623910

RESUMEN

Diversified molecular information-processing methods have significant implications for nanoscale manipulation and control, monitoring and disease diagnosis of organisms, and direct intervention in biological activities. However, as an effective approach for implementing multifunctional molecular information processing, DNA reaction networks (DRNs) with numerous functionally specialized molecular structures have challenged them on scale design, leading to increased network complexity, further causing problems such as signal leakage, attenuation, and cross-talk in network reactions. Our study developed a strategy for performing various signal-processing tasks through engineering modular DRNs. This strategy is based on a universal core unit with signal selection capability, and a time-adjustable signal self-resetting module is achieved by combing the core unit and self-resetting unit, which improves the time controllability of modular DRNs. In addition, multi-input and -output signal cross-catalytic and continuously adjustable signal delay modules were realized by combining core and threshold units, providing a flexible, precise method for modular DRNs to process the signal. The strategy simplifies the design of DRNs, helps generate design ideas for large-scale integrated DRNs with multiple functions, and provides prospects in biocomputing, gene regulation, and biosensing.


Asunto(s)
ADN , ADN/química , Técnicas Biosensibles/métodos
5.
Analyst ; 149(4): 1327-1336, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38259145

RESUMEN

Biological contamination is an important issue in environmental pH detection, and our prepared electrochemically cleanable electrode may be an effective solution. By electrodepositing an iridium oxide-ruthenium oxide composite on a titanium sheet substrate, the electrode shows a sensitivity of 59.4 mV per pH in the pH range of 2-12 with high reproducibility, low hysteresis, high selectivity and high stability. It is worth mentioning that the electrode was proved to be electrochemically cleanable from biological contamination. When the cleaning time was 30 minutes, the electrode sensitivity rose from 50 to 58 mV per pH. Furthermore, the pH sensor, assembled from the prepared iridium-ruthenium oxide electrode and a home-made Ag/AgCl electrode, has similar electrode properties to those of commercial glass electrodes, but is also mechanically strong and electrochemically cleanable, which is promising for long-term deployment in natural environments.

6.
Environ Sci Technol ; 58(6): 3041-3053, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38291736

RESUMEN

Typically, SO2 unavoidably deactivates catalysts in most heterogeneous catalytic oxidations. However, for Pt-based catalysts, SO2 exhibits an extraordinary boosting effect in propane catalytic oxidation, but the promotive mechanism remains contentious. In this study, an in situ-formed tactful (Pt-S-O)-Ti structure was concluded to be a key factor for Pt/TiO2 catalysts with a substantial SO2 tolerance ability. The experiments and theoretical calculations confirm that the high degree of hybridization and orbital coupling between Pt 5d and S 3p orbitals enable more charge transfer from Pt to S species, thus forming the (Pt-S-O)-Ti structure with the oxygen atom dissociated from the chemisorbed O2 adsorbed on oxygen vacancies. The active oxygen atom in the (Pt-S-O)-Ti active structure is a robust site for C3H8 adsorption, leading to a better C3H8 combustion performance. This work can provide insights into the rational design of chemical bonds for high SO2 tolerance catalysts, thereby improving economic and environmental benefits.


Asunto(s)
Oxígeno , Titanio , Titanio/química , Oxidación-Reducción , Catálisis , Adsorción
7.
Child Dev ; 95(4): 1351-1366, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38297823

RESUMEN

The longitudinal person-oriented study aimed to explore profiles, stability, gender differences, and compositional relations of math attitudes by tracking Chinese third graders (Ntotal = 1013, Mage(T1) = 8.92 ± 0.46, Ngirls = 404) in four waves with 1-year intervals. Five profiles and unstable transitional probabilities were identified among the four waves. The relations between enjoyment to confidence and value shifted from reciprocity to enjoyment dominance, but value negatively predicted later enjoyment and confidence. Additionally, boys' advantages were significant in late elementary school (fifth, sixth grades) and girls benefited from initial positive attitudes. These findings suggest that Chinese students' math attitudes in middle childhood are unstable, shaped by internal and external environmental dynamics, and need to be further explored in cross-cultural research.


Asunto(s)
Actitud , Matemática , Instituciones Académicas , Humanos , Femenino , Masculino , Niño , Estudios Longitudinales , China , Factores Sexuales , Placer/fisiología
8.
Neurobiol Dis ; 180: 106069, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36893902

RESUMEN

Deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major depression, and suggests that the LHb might be an effective target of DBS therapy for depression. Here, we found that DBS in the LHb effectively decreased depression-like behaviors in rats experienced with chronic unpredictable mild stress (CUMS), a well-accepted paradigm for modeling depression in rodents. In vivo electrophysiological recording unveiled that CUMS increased neuronal burst firing, as well as the proportion of neurons showing hyperactivity to aversive stimuli in the LHb. Nevertheless, DBS downregulated local field potential power, reversed the CUMS-induced increase of LHb burst firing and neuronal hyperactivity to aversive stimuli, and decreased the coherence between LHb and ventral tegmental area (VTA). Our results demonstrate that DBS in the LHb exerts antidepressant-like effects and reverses local neural hyperactivity, supporting the LHb as a target of DBS therapy for depression.


Asunto(s)
Estimulación Encefálica Profunda , Trastorno Depresivo , Habénula , Ratas , Animales , Depresión/terapia , Estimulación Encefálica Profunda/métodos , Neuronas
9.
Opt Express ; 31(9): 13585-13600, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37157243

RESUMEN

Optical aberrations of optical systems cause significant degradation of imaging quality. Aberration correction by sophisticated lens designs and special glass materials generally incurs high cost of manufacturing and the increase in the weight of optical systems, thus recent work has shifted to aberration correction with deep learning-based post-processing. Though real-world optical aberrations vary in degree, existing methods cannot eliminate variable-degree aberrations well, especially for the severe degrees of degradation. Also, previous methods use a single feed-forward neural network and suffer from information loss in the output. To address the issues, we propose a novel aberration correction method with an invertible architecture by leveraging its information-lossless property. Within the architecture, we develop conditional invertible blocks to allow the processing of aberrations with variable degrees. Our method is evaluated on both a synthetic dataset from physics-based imaging simulation and a real captured dataset. Quantitative and qualitative experimental results demonstrate that our method outperforms compared methods in correcting variable-degree optical aberrations.

10.
Biol Res ; 56(1): 48, 2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37608294

RESUMEN

BACKGROUND: To elucidate the role of Mucin1 (MUC1) in the trophoblast function (glucose uptake and apoptosis) of gestational diabetes mellitus (GDM) women through the Wnt/ß-catenin pathway. METHODS: Glucose uptake was analyzed by plasma GLUT1 and GLUT4 levels with ELISA and measured by the expression of GLUT4 and INSR with immunofluorescence and Western blotting. Apoptosis was measured by the expression of Bcl-2 and Caspase3 by Western blotting and flow cytometry. Wnt/ß-catenin signaling measured by Western blotting. In vitro studies were performed using HTR-8/SVneo cells that were cultured and treated with high glucose (HG), sh-MUC1 and FH535 (inhibitor of Wnt/ß-catenin signaling). RESULTS: MUC1 was highly expressed in the placental trophoblasts of GDM, and the Wnt/ß-catenin pathway was activated, along with dysfunction of glucose uptake and apoptosis. MUC1 knockdown resulted in increased invasiveness and decreased apoptosis in trophoblast cells. The initial linkage between MUC1, the Wnt/ß-catenin pathway, and glucose uptake was confirmed by using an HG-exposed HTR-8/SVneo cell model with MUC1 knockdown. MUC1 knockdown inhibited the Wnt/ß-catenin signaling pathway and reversed glucose uptake dysfunction and apoptosis in HG-induced HTR-8/SVneo cells. Meanwhile, inhibition of Wnt/ß-catenin signaling could also reverse the dysfunction of glucose uptake and apoptosis. CONCLUSIONS: In summary, the increased level of MUC1 in GDM could abnormally activate the Wnt/ß-catenin signaling pathway, leading to trophoblast dysfunction, which may impair glucose uptake and induce apoptosis in placental tissues of GDM women.


Asunto(s)
Diabetes Gestacional , Trofoblastos , Embarazo , Humanos , Femenino , Vía de Señalización Wnt , beta Catenina , Placenta , Glucosa
11.
Ophthalmic Res ; 66(1): 1300-1307, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37812921

RESUMEN

INTRODUCTION: This real-world study evaluated the efficacy, safety, and operative parameters of two perfluoropropane (C3F8) tamponade methods combined with pars plana vitrectomy (PPV) for retinal detachment (RD). METHODS: A retrospective study of 132 patients (132 eyes) with RD (pure C3F8 in 38 eyes, mixed C3F8 in 94 eyes). All eyes underwent PPV with C3F8 tamponade and were followed up for at least 3 months. Retinal reattachment rate, time of gas configuration and injection, C3F8 dosage, intraocular pressure (IOP), best corrected visual acuity, postoperative ocular inflammation, and patients' complaints were evaluated. RESULTS: The single-surgery retinal reattachment rates of the pure C3F8 group and mixed C3F8 group were 97.4% and 96.8%, respectively, with no significant difference (p = 1.00). The final retinal reattachment rates of the two groups were 100% and 97.2%, respectively, with no significant difference (p = 1.00). The gas configuration time, gas injection time, and C3F8 dosage were significantly less in the pure C3F8 group (all p < 0.001). Time, but not group, was the influencing factor of postoperative IOP changes in the two groups (p < 0.001, p = 0.547, respectively). Compared with the baseline, the IOP estimates of the pure C3F8 group showed a significant increase immediately after surgery (p < 0.001), and the mixed C3F8 group showed a significant increase immediately and 1-2 days after surgery (all p < 0.05). There was no statistical difference in ocular inflammation (p = 0.339) and patients' complaints of discomfort (p = 0.175) between the two groups. CONCLUSION: Both the two methods of C3F8 tamponade combined with PPV in RD patients showed good efficacy and safety, but the clinical operation of pure C3F8 tamponade was more convenient and eco-friendly.


Asunto(s)
Desprendimiento de Retina , Perforaciones de la Retina , Humanos , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/cirugía , Vitrectomía/métodos , Estudios Retrospectivos , Retina , Inflamación , Perforaciones de la Retina/cirugía
12.
Int J Mol Sci ; 24(12)2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37373138

RESUMEN

Pectobacterium spp. infect many horticultural crops worldwide and lead to serious crop losses. Zinc-uptake-regulator (Zur) proteins are present widely in prokaryotes and play an important role in pathogenicity. To uncover the role of Zur in P. odoriferum, we constructed mutant (ΔZur) and overexpression [Po (Zur)] strains of a Zur, and a virulence assay showed that the Po (Zur) was of significantly lower virulence, while the ΔZur displayed significantly increased virulence on Chinese cabbage compared to their respective control strains, wild-type P. odoriferum (Po WT) and P. odoriferum harboring an empty vector (Po (EV)) (p < 0.05). The growth curves of the ΔZur and Po (Zur) showed no obvious differences from those of the control strains. Comparative transcriptome analysis showed that Zur overexpression in P. odoriferum induced differentially expressed genes (DEGs) related to flagellum and cell motility, while mutating Zur resulted in DEGs mainly corresponding to divalent-metal-ion transport and membrane transport. Phenotypic experiments on the Po (Zur) showed that flagellum numbers and cell motility were reduced in comparison with the control, while those of the ΔZur did not change. Collectively, these results show that the Zur negatively regulates the virulence of P. odoriferum and might function via a dual mechanism dependent on dose.


Asunto(s)
Proteínas Bacterianas , Pectobacterium , Virulencia/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Zinc/metabolismo , Transporte Iónico , Pectobacterium/genética , Pectobacterium/metabolismo , Regulación Bacteriana de la Expresión Génica
13.
Int J Mol Sci ; 24(18)2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37762124

RESUMEN

Chronic pain is a significant health problem worldwide. Recent evidence has suggested that the ventral hippocampus is dysfunctional in humans and rodents, with decreased neuronal excitability and connectivity with other brain regions, parallel pain chronicity, and persistent nociceptive hypersensitivity. But the molecular mechanisms underlying hippocampal modulation of pain remain poorly elucidated. In this study, we used ex vivo whole-cell patch-clamp recording, immunofluorescence staining, and behavioral tests to examine whether hyperpolarization-activated cyclic nucleotide-gated channels 2 (HCN2) in the ventral hippocampal CA1 (vCA1) were involved in regulating nociceptive perception and CFA-induced inflammatory pain in mice. Reduced sag potential and firing rate of action potentials were observed in vCA1 pyramidal neurons from CFA-injected mice. Moreover, the expression of HCN2, but not HCN1, in vCA1 decreased in mice injected with CFA. HCN2 knockdown in vCA1 pyramidal neurons induced thermal hypersensitivity, whereas overexpression of HCN2 alleviated thermal hyperalgesia induced by intraplantar injection of CFA in mice. Our findings suggest that HCN2 in the vCA1 plays an active role in pain modulation and could be a promising target for the treatment of chronic pain.


Asunto(s)
Dolor Crónico , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Canales de Potasio , Animales , Ratones , Potenciales de Acción , Canales Catiónicos Regulados por Nucleótidos Cíclicos/metabolismo , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Nocicepción , Canales de Potasio/genética , Canales de Potasio/metabolismo , Región CA1 Hipocampal/metabolismo
14.
Pharm Biol ; 61(1): 746-754, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37177984

RESUMEN

CONTEXT: Daphnetin is a natural product with anti-inflammatory, antioxidant, and neuroprotective properties. Reports have found that it has a strong analgesic effect; however, its analgesic mechanism is unknown. OBJECTIVE: We explored the effect and mechanism of daphnetin on neuropathic pain (NP). MATERIALS AND METHODS: The rat model of NP was established by ligation of the sciatic nerve. Male Sprague-Dawley rats were divided into six groups: Control, Model, Sham, morphine (0.375 mg/kg), and daphnetin (0.0625 and 0.025 mg/kg). Rats were intrathecally injected with drugs or normal saline once daily for three days. Hyperalgesia was evaluated by mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). Protein levels were detected using ELISA, immunofluorescence, and western blotting. RESULTS: Compared to the Model group, daphnetin improved TWT (46.70 °C vs. 42.20 °C) and MWT (45.60 g vs. 23.60 g), reduced the expression of interleukin-1ß (0.99 ng/g vs. 1.42 ng/g), interleukin-6 (0.90 ng/g vs. 1.52 ng/g), and tumor necrosis factor-α (0.93 ng/g vs. 1.52 ng/g) in the sciatic nerve. Daphnetin decreased the expression of toll-like receptor 4 (TLR4) (0.47-fold), phosphorylated inhibitor of NF-κB (p-IKBα) (0.29-fold), nuclear factor kappaB (NF-κB) (0.48-fold), glial fibrillary acidic protein (GFAP) (0.42-fold), CXC chemokine ligand type 1 (CXCL1) (0.84-fold), CXC chemokine receptor type 2 (CXCR2) (0.78-fold) in the spinal cord. DISCUSSION AND CONCLUSIONS: Daphnetin alleviates NP by inhibiting inflammation and astrocyte activation in the spinal cord, providing theoretical support for the extensive clinical treatment of NP.


Asunto(s)
FN-kappa B , Neuralgia , Ratas , Masculino , Animales , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Analgésicos/farmacología , Analgésicos/uso terapéutico , Médula Espinal , Neuralgia/tratamiento farmacológico , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/farmacología
15.
Development ; 146(6)2019 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-30683662

RESUMEN

Canonical Wnts promote myoblast differentiation; however, the role of ß-catenin in adult myogenesis has been contentious, and its mechanism(s) unclear. Using CRISPR-generated ß-catenin-null primary adult mouse myoblasts, we found that ß-catenin was essential for morphological differentiation and timely deployment of the myogenic gene program. Alignment, elongation and fusion were grossly impaired in null cells, and myogenic gene expression was not coordinated with cytoskeletal and membrane remodeling events. Rescue studies and genome-wide analyses extended previous findings that a ß-catenin-TCF/LEF interaction is not required for differentiation, and that ß-catenin enhances MyoD binding to myogenic loci. We mapped cellular pathways controlled by ß-catenin and defined novel targets in myoblasts, including the fusogenic genes myomaker and myomixer. We also showed that interaction of ß-catenin with α-catenin was important for efficient differentiation. Overall the study suggests dual roles for ß-catenin: a TCF/LEF-independent nuclear function that coordinates an extensive network of myogenic genes in cooperation with MyoD; and an α-catenin-dependent membrane function that helps control cell-cell interactions. ß-Catenin-TCF/LEF complexes may function primarily in feedback regulation to control levels of ß-catenin and thus prevent precocious/excessive myoblast fusion.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Proteína MioD/metabolismo , Mioblastos/metabolismo , alfa Catenina/metabolismo , beta Catenina/metabolismo , Animales , Diferenciación Celular , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Cromatina/metabolismo , Citoesqueleto/metabolismo , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Genómica , Células HEK293 , Humanos , Ratones , Desarrollo de Músculos , Fenotipo , Regiones Promotoras Genéticas , Transducción de Señal , Transcriptoma , Transfección , Proteínas Wnt/metabolismo
16.
Rapid Commun Mass Spectrom ; 36(1): e9205, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34636119

RESUMEN

RATIONALE: Salvianolic acid B (Sal B), the Q-marker in Salvia miltiorrhiza, was proved to present an obvious anti-diabetes effect when treated as a food intake. Until now, the metabolism feature, tissue distribution and anti-diabetes mechanism of Sal B have not been fully elucidated. METHODS: The metabolites of Sal B in rats were profiled using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-diabetes mechanism of Sal B was predicted by network pharmacology. RESULTS: A total of 31 metabolites were characterized in rats after ingestion of Sal B at a dosage of 40 mg/kg, including 1 in plasma, 19 in urine, 31 in feces, 0 in heart, 0 in liver, 0 in spleen, 1 in lung, 1 in kidney and 0 in brain. Among them, 18 metabolites were reported for the first time. Phase I reactions of hydrolysis, hydrogenation, dehydroxylation, hydroxylation, decarboxylation and isomerization, and phase II reactions of methylation were found in Sal B. Notably, decarboxylation and dehydroxylation were revealed in Sal B for the first time. The pharmacology network results showed that Sal B and its metabolites could regulate ALB, PLG, ACE, CASP3, MMP9, MMP2, MTOR, etc. The above targets were involved in insulin signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, etc. CONCLUSIONS: The metabolism feature of Sal B in vivo was systematically revealed, and its anti-diabetes mechanism for further pharmacological validations was predicted based on metabolite profiling and network pharmacology for the first time.


Asunto(s)
Benzofuranos/farmacocinética , Diabetes Mellitus/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacocinética , Hipoglucemiantes/farmacocinética , Animales , Benzofuranos/administración & dosificación , Benzofuranos/química , Caspasas/genética , Caspasas/metabolismo , Cromatografía Líquida de Alta Presión , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Heces/química , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Isomerismo , Riñón/química , Riñón/metabolismo , Hígado/química , Hígado/metabolismo , Pulmón/química , Pulmón/metabolismo , Masculino , Espectrometría de Masas , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Farmacología en Red , Ratas , Salvia miltiorrhiza/química
17.
Clin Exp Pharmacol Physiol ; 49(5): 567-576, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35147244

RESUMEN

Thrombin has long been considered a desirable antithrombotic target, but anti-thrombin therapy without anti-platelet therapy has never achieved the ideal effect. HY023016, derived from dabigatran etexilate, exhibited a potent antithrombotic efficacy. In the present study, mechanisms underlying this effect were explored. HY023016 strongly decreased the binding of thrombin to recombinant GPIbα N-terminal sequence, which was confirmed by surface plasmon resonance. Flow cytometry revealed that HY023016 selectively decreased the binding of antibody to GPIbα and inhibited the washed human platelet aggregation induced by thrombin. Fluorescence experiment showed that HY023016 remarkably inhibited exosite II by a loss of affinity for the γ'-peptide of fibrinogen. Using intravital microscopy, we observed and recorded the dynamic process of thrombus formation and found that HY023016 effectively prevented thrombus formation in rat arteriovenous shunt thrombosis model. On the basis of these findings, we propose that HY023016 provides a novel insight into the antithrombotic mechanism, which exerts synergistic anticoagulant and antiplatelet effects through thrombin and GPIbα.


Asunto(s)
Dabigatrán , Fibrinolíticos , Animales , Anticoagulantes , Dabigatrán/farmacología , Dabigatrán/uso terapéutico , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Ratas , Trombina/metabolismo
18.
Pain Manag Nurs ; 23(1): 26-30, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34756521

RESUMEN

BACKGROUND: To investigate the pain and self-management status of patients with cancer and the influencing factors of pain and self-management status during the COVID-19 pandemic. METHODS: A cross-sectional design was used. Eighty-one Chinese patients with cancer were recruited in December 2020. The Brief Pain Inventory, the Pain Management Inventory, and the Pain Self-efficacy Questionnaire were used to evaluate patients' pain and self-management status. Descriptive statistical analysis and multiple linear regression models were conducted for the research aims. RESULTS: Two thirds of the participants experienced moderate to severe pain. Cancer pain had moderate to severe interference on 90.12% of patients' lives. Self-management of pain in these participants was low. The most commonly used methods of pain management included adjusting activity intensity to avoid fatigue, using distraction techniques, and massaging the sore area. The most effective methods to manage pain included taking analgesics prescribed by doctor, taking over-the-counter analgesics, and massaging the sore area. Fifteen patients (18.5%) believed that the COVID-19 pandemic had an impact on pain management and 26 patients (32.1%) needed support. Pain education, pain interference on sleep, chemotherapy, and payment status were significantly associated with cancer patients 'pain self-management. CONCLUSIONS: During the COVID-19 pandemic, patients with cancer had moderate to severe pain intensity with low levels of self-management and self-efficacy towards that pain.


Asunto(s)
COVID-19 , Neoplasias , Automanejo , China/epidemiología , Estudios Transversales , Humanos , Neoplasias/complicaciones , Neoplasias/terapia , Dolor/tratamiento farmacológico , Dolor/epidemiología , Pandemias , SARS-CoV-2
19.
Int J Mol Sci ; 23(15)2022 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-35955961

RESUMEN

The Dlk1-Dio3 imprinted domain on mouse chromosome 12 contains three well-characterized paternally methylated differentially methylated regions (DMRs): IG-DMR, Gtl2-DMR, and Dlk1-DMR. These DMRs control the expression of many genes involved in embryonic development, inherited diseases, and human cancer in this domain. The first maternal methylation DMR discovered in this domain was the Meg8-DMR, the targets and biological function of which are still unknown. Here, using an enhancer-blocking assay, we first dissected the functional parts of the Meg8-DMR and showed that its insulator activity is dependent on the CCCTC-binding factor (CTCF) in MLTC-1. Results from RNA-seq showed that the deletion of the Meg8-DMR and its compartment CTCF binding sites, but not GGCG repeats, lead to the downregulation of numerous genes on chromosome 12, in particular the drastically reduced expression of Dlk1 and Rtl1 in the Dlk1-Dio3 domain, while differentially expressed genes are enriched in the MAPK pathway. In vitro assays revealed that the deletion of the Meg8-DMR and CTCF binding sites enhances cell migration and invasion by decreasing Dlk1 and activating the Notch1-Rhoc-MAPK/ERK pathway. These findings enhance research into gene regulation in the Dlk1-Dio3 domain by indicating that the Meg8-DMR functions as a long-range regulatory element which is dependent on CTCF binding sites and affects multiple genes in this domain.


Asunto(s)
Impresión Genómica , ARN Largo no Codificante , Animales , Sitios de Unión , Proteínas de Unión al Calcio/genética , Metilación de ADN , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Embarazo , ARN Largo no Codificante/genética
20.
Am J Physiol Cell Physiol ; 321(6): C992-C999, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34705585

RESUMEN

Thirst is an important interoceptive response and drives water consumption. The hippocampus actively modulates food intake and energy metabolism, but direct evidence for the exact role of the hippocampus in modulating drinking behaviors is lacking. We observed decreased number of c-Fos-positive neurons in the ventral hippocampal CA1 (vCA1) after water restriction or hypertonic saline injection in rats. Suppressed vCA1 neuronal activities under the hypertonic state were further confirmed with in vivo electrophysiological recording, and the level of suppression paralleled both the duration and the total amount of water consumption. Chemogenetic inhibition of vCA1 pyramidal neurons increased water consumption in rats injected with both normal and hypertonic saline. These findings suggest that suppression of vCA1 pyramidal neuronal activities enhances water intake.


Asunto(s)
Potenciales de Acción/fisiología , Región CA1 Hipocampal/fisiología , Ingestión de Líquidos/fisiología , Células Piramidales/fisiología , Solución Salina Hipertónica/administración & dosificación , Potenciales de Acción/efectos de los fármacos , Animales , Región CA1 Hipocampal/efectos de los fármacos , Ingestión de Líquidos/efectos de los fármacos , Masculino , Células Piramidales/efectos de los fármacos , Ratas , Ratas Wistar
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