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1.
J Chem Phys ; 160(11)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38506296

RESUMO

Using ab initio nonadiabatic molecular dynamics, we study the effect of large A-site cations on nonradiative electron-hole recombination in two-dimensional Ruddlesden-Popper perovskites HA2APb2I7, HA = n-hexylammonium, A = methylammonium (MA), or guanidinium (GA). The steric hindrance created by large GA cations distorts and stiffens the inorganic Pb-I lattice, reduces thermal structural fluctuations, and maintains the delocalization of electrons and holes at ambient and elevated temperatures. The delocalized charges interact more strongly in the GA system than in the MA system, and the charge recombination is accelerated. In contrast, replacement of only some MA cations with GA enhances disorder and increases charge lifetime, as seen in three-dimensional perovskites. This study highlights the key influence of structural fluctuations and disorder on the properties of charge carriers in metal halide perovskites, providing guidance for tuning materials' optoelectronic performance.

2.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39034149

RESUMO

OBJECTIVES: To investigate the incidence and influencing factors of allergic reactions to cephalosporins. METHODS: A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021. The incidence of allergic reactions to cephalosporins was investigated. The influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression. RESULTS: A total of 56 155 patients were included in this study. The total incidence of allergic reactions to cephalosporin was 1.67 ‰, the highest incidences of anaphylaxis occurred in ceftizoxime (4.27‰), followed by ceftriaxone (3.49‰) and cefotaxime (2.40‰). There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests (1.75‰ vs. 1.63‰, RR=1.07, 95%CI:0.70-1.63, P> 0.05). Poisson regression showed that body mass index (BMI) <18.5 kg/cm2 (RR=2.43, 95%CI: 1.23-4.82, P<0.01) and history of ß-lactam antibiotics allergy (RR=33.88, 95%CI: 1.47-781.12, P<0.05) increased cephalosporin-induced anaphylaxis. Compared with cefuroxime, the risk of allergic reactions was increased for ceftriaxone (RR=3.08, 95%CI: 1.70-5.59, P<0.01), ceftazidime (RR=1.89, 95%CI: 1.03-3.47, P<0.05), and ceftriaxone (RR=3.74, 95%CI: 1.64-8.50, P<0.01). CONCLUSIONS: Lower BMI and history of ß-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions, and the routine skin test may not reduce the occurrence of allergic reactions to cephalosporins.

3.
Mol Cell Biochem ; 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37542599

RESUMO

Cardiovascular disease, especially myocardial infarction, is a serious threat to human health. Many drugs currently used cannot achieve the desired therapeutic effect due to the lack of selectivity. With the in-depth understanding of the role of microRNA (miRNA) in cardiovascular disease and the wide application of nanotechnology, loading drugs into nanoparticles with the help of nano-delivery system may have a better effect in the treatment of cardiomyopathy. In this review, we highlight the latest research on miRNAs in the treatment of cardiovascular disease in recent years and discuss the possibilities and challenges of using miRNA to treat cardiomyopathy. Secondly, we discuss the delivery of miRNA through different nano-carriers, especially inorganic, polymer and liposome nano-carriers. The preparation of miRNA nano-drugs by encapsulating miRNA in these nano-materials will provide a new treatment option. In addition, the research status of miRNA in the treatment of cardiomyopathy based on nano-carriers is summarized. The use of this delivery tool cannot only realize therapeutic potential, but also greatly improve drug targeting and reduce side effects.

4.
Chem Biodivers ; 18(2): e2000856, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33295037

RESUMO

Dioscorea polystachya, named Chinese yam, is widely cultivated as a functional food and natural medicine in China. There is currently little information about the chemical characteristics of Dioscorea polystachya in different organs (tuber cortex and tuber flesh) and at various ages. In this study, an ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used to profile chemical compounds in Dioscorea polystachya. As a result, thirty-eight compounds were detected in yam tuber cortex and tuber flesh. More compounds were detected in yam tuber cortex than in tuber flesh. Compounds such as dehydroepiandrosterone, allantoin and flavonoids were selected as biomarker candidates. Dehydroepiandrosterone was found more abundant in tuber flesh, while allantoin and flavonoids showed higher levels in tuber cortex. Furthermore, the levels of dioscin, malvalic acid and sucrose differed significantly among age groups and were highest in the tubers at 2 years. While the levels of allantoin, adenosine and glutamine increased with the growing years and were highest at 4 years. Thus, 2-year old Dioscorea polystachya tubers could be harvested to prepare dioscin, malvalic acid and sucrose supplements. The 4-year-old Dioscorea polystachya tubers would be the best choice for obtaining a large amount of allantoin and adenosine in industrial production.


Assuntos
Dioscorea/química , Tubérculos/química , Alantoína/análise , Cromatografia Líquida de Alta Pressão/métodos , Desidroepiandrosterona/análise , Dioscorea/crescimento & desenvolvimento , Flavonoides/análise , Espectrometria de Massas/métodos , Tubérculos/crescimento & desenvolvimento
5.
Chem Biodivers ; 16(10): e1900363, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385642

RESUMO

In this study, the metabolite profiling of three different parts of Crocus sativus L. was measured by using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTof-MS/MS). Multivariate statistical analysis was used to distinguish among the samples from different parts. A total of 54 compounds were identified in tepals, stigmas and stamens by UPLC-QTof-MS/MS. The results stated that chemical characteristics of saffron were obviously diverse in terms of the parts of flower. Through analysis, coniferin and crocin-2 were special components in stigmas when compared to tepals and stamens. The content of flavonoids was high in tepals when compared with the stigmas. The tepal of saffron may processed as a source of flavonoids in the future. The research provided the basis for the theory that only the stigma can be used as medicine.


Assuntos
Crocus/química , Flavonoides/análise , Flores/química , Metabolômica , Cromatografia Líquida de Alta Pressão , Crocus/metabolismo , Flavonoides/metabolismo , Flores/metabolismo , Espectrometria de Massas em Tandem
6.
BMC Plant Biol ; 17(1): 119, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28693426

RESUMO

BACKGROUND: Among CESA-like gene superfamily, the cellulose synthase-like D (CSLD) genes are most similar to cellulose synthase genes and have been reported to be involved in tip-growing cell and stem development. However, there has been no genome-wide characterization of this gene subfamily in cotton. We thus sought to analyze the evolution and functional characterization of CSLD proteins in cotton based on fully sequenced cotton genomes. RESULTS: A total of 23 full-length CSLD proteins were identified in Gossypium raimondii, Gossypium arboreum and Gossypium hirsutum. The phylogenetic tree divided the CSLD proteins into five clades with strong support: CSLD1, CSLD2/3, CSLD4, CSLD5 and CSLD6. The total expression of GhCSLD genes was the highest in androecium & gynoecium (mostly contributed by CSLD1 and CSLD4) compared with other CSL genes. CSLD1 and CSLD4 were only highly expressed in androecium & gynoecium (A&G), and showed tissue-specific expression. The total expression of CSLD2/3, 5 and 6 was highest in the specific tissues. These results suggest that CSLD genes showed the different pattern of expression. Cotton CSLD proteins were subjected to different evolutionary pressures, and the CSLD1 and CSLD4 proteins exhibited episodic and long-term shift positive selection. The predicted three-dimensional structure of GrCSLD1 suggested that GrCSLD1 belongs to glycosyltransferase family 2. The amino acid residues under positive selection in the CSLD1 lineage are positioned in a region adjacent to the class-specific region (CSR), ß1-strand and transmembrane helices (TMHs) in the GrCSLD1structure. CONCLUSION: Our results characterized the CSLD proteins by an integrated approach containing phylogeny, transcriptional profiling and 3D modeling. The study added to the understanding about the importance of the CSLD family and provide a useful reference for selecting candidate genes and their associations with the biosynthesis of the cell wall in cotton.


Assuntos
Evolução Molecular , Gossypium/genética , Família Multigênica , Proteínas de Plantas/genética , Perfilação da Expressão Gênica , Genoma de Planta , Glicosiltransferases/genética , Gossypium/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Conformação Proteica , Seleção Genética
7.
J Biol Chem ; 290(40): 24438-52, 2015 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-26253172

RESUMO

The steroid hormone ecdysone, which controls insect molting and metamorphosis, is synthesized in the prothoracic gland (PG), and several steroidogenic enzymes that are expressed specifically in the PG are involved in ecdysteroidogenesis. In this study, we identified new regulators that are involved in the transcriptional control of the silkworm steroidogenic enzyme genes. In silico analysis predicted several potential cis-regulatory elements (CREs) for the homeodomain transcription factors Antennapedia (Antp) and POU-M2 in the proximal promoters of steroidogenic enzyme genes. Antp and POU-M2 are expressed dynamically in the PG during larval development, and their overexpression in silkworm embryo-derived (BmE) cells induced the expression of steroidogenic enzyme genes. Importantly, luciferase reporter analyses, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays revealed that Antp and POU-M2 promote the transcription of the silkworm steroidogenic enzyme gene Phantom (Phm) by binding directly to specific motifs within overlapping CREs in the Phm promoter. Mutations of these CREs in the Phm promoter suppressed the transcriptional activities of both Antp and POU-M2 in BmE cells and decreased the activities of mutated Phm promoters in the silkworm PG. In addition, pulldown and co-immunoprecipitation assays demonstrated that Antp can interact with POU-M2. Moreover, RNA interference-mediated down-regulation of either Antp or POU-M2 during silkworm wandering not only decreased the ecdysone titer but also led to the failure of metamorphosis. In summary, our results suggest that Antp and POU-M2 coordinate the transcription of the silkworm Phm gene directly, indicating new roles for homeodomain proteins in regulating insect ecdysteroidogenesis.


Assuntos
Proteína do Homeodomínio de Antennapedia/metabolismo , Proteínas de Helminto/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Insetos/metabolismo , Metamorfose Biológica , Oxigenases de Função Mista/metabolismo , Fatores do Domínio POU/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Animais , Proteína do Homeodomínio de Antennapedia/genética , Bombyx , Biologia Computacional , Ecdisona/química , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Helminto/genética , Proteínas de Homeodomínio/genética , Proteínas de Insetos/genética , Oxigenases de Função Mista/genética , Muda , Mutação , Nucleopoliedrovírus/genética , Fatores do Domínio POU/genética , Regiões Promotoras Genéticas , Ligação Proteica , Mapeamento de Interação de Proteínas , Estrutura Terciária de Proteína , Interferência de RNA , Fatores de Transcrição/genética
8.
Biochim Biophys Acta ; 1844(10): 1729-40, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25017878

RESUMO

Eph-ephrin interactions control the signal transduction between cells and play an important role in carcinogenesis and other diseases. The interactions between Eph receptors and ephrins of the same subclass are promiscuous; there are cross-interactions between some subclasses, but not all. To understand how Eph-ephrin interactions can be both promiscuous and specific, we investigated sixteen energy landscapes of four Eph receptors (A2, A4, B2, and B4) interacting with four ephrin ligands (A1, A2, A5, and B2). We generated conformational ensembles and recognition energy landscapes starting from separated Eph and ephrin molecules and proceeding up to the formation of Eph-ephrin complexes. Analysis of the Eph-ephrin recognition trajectories and the co-evolution entropy of 400 ligand binding domains of Eph receptor and 241 ephrin ligands identified conserved residues during the recognition process. Our study correctly predicted the promiscuity and specificity of the interactions and provided insights into their recognition. The dynamic conformational changes during Eph-ephrin recognition can be described by progressive conformational selection and population shift events, with two dynamic salt bridges between EphB4 and ephrin-B2 contributing to the specific recognition. EphA3 cancer-related mutations lowered the binding energies. The specificity is not only controlled by the final stage of the interaction across the protein-protein interface, but also has large contributions from binding kinetics with the help of dynamic intermediates along the pathway from the separated Eph and ephrin to the Eph-ephrin complex.

9.
Int J Mol Sci ; 16(11): 26166-85, 2015 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26540044

RESUMO

The silkworm Dominant trimolting (Moltinism, M³) mutant undergoes three larval molts and exhibits precocious metamorphosis. In this study, we found that compared with the wild-type (WT) that undergoes four larval molts, both the juvenile hormone (JH) concentration and the expression of the JH-responsive gene Krüppel homolog 1 (Kr-h1) began to be greater in the second instar of the M³ mutant. A positional cloning analysis revealed that only the homeodomain transcription factor gene Sex combs reduced (Scr) is located in the genomic region that is tightly linked to the M³ locus. The expression level of the Scr gene in the brain-corpora cardiaca-corpora allata (Br-CC-CA) complex, which controls the synthesis of JH, was very low in the final larval instar of both the M³ and WT larvae, and exhibited a positive correlation with JH titer changes. Importantly, luciferase reporter analysis and electrophoretic mobility shift assay (EMSA) demonstrated that the Scr protein could promote the transcription of genes involved in JH biosynthesis by directly binding to the cis-regulatory elements (CREs) of homeodomain protein on their promoters. These results conclude that the homeodomain protein Scr is transcriptionally involved in the regulation of JH biosynthesis in the silkworm.


Assuntos
Bombyx/genética , Bombyx/metabolismo , Regulação da Expressão Gênica , Hormônios Juvenis/biossíntese , Transcrição Gênica , Quinases da Família src/metabolismo , Animais , Mapeamento Cromossômico , Mutação , Fenótipo , Regiões Promotoras Genéticas , Ligação Proteica , Locos de Características Quantitativas , Quinases da Família src/genética
10.
Chem Commun (Camb) ; 60(3): 316-319, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38063025

RESUMO

This study presents an injectable cell-laden hydrogel system based on silk acid, a carboxylated derivative of natural silk fibroin, which exhibits promising applications in biomedicine. The hydrogel is produced under physiological conditions (37 °C and pH 7.4) via physical crosslinking. Notably, the hydrogel demonstrates remarkable cytocompatibility, enabling efficient cell encapsulation, and exhibits good injectability. These promising results strongly indicate the potential of silk acid hydrogel for transformative applications, including 3D cell culture, targeted cell delivery, and tissue engineering.


Assuntos
Fibroínas , Hidrogéis , Seda , Engenharia Tecidual/métodos
11.
Medicine (Baltimore) ; 103(36): e39551, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252227

RESUMO

BACKGROUND: This study aimed to investigate the effects of meticulous nursing care (MNC) for patients with coronary heart disease undergoing coronary CT angiography (CCTA). METHODS: We conducted a comprehensive search of the Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure, and Wangfang databases from inception to January 1, 2024. Randomized clinical trials (RCTs) evaluating the effects of MNC for CCTA were included. Outcomes assessed included self-rating anxiety scale (SAS), self-rating depression scale (SDS), overall satisfaction of nursing care (OSNC), examination time (ET, min), radiation dose received (RDR, mSv), breathing control time (BCT), and heart rate control time (HRCT).The methodological quality of all included RCTs was evaluated using the Cochrane risk-of-bias tool, while statistical analysis was conducted using RevMan 5.4 software. RESULTS: Six eligible trials involving 1064 patients were included. The results of the meta-analysis showed significant differences in SAS (MD = -2.84, 95% CI [-3.31, -2.37], I2 = 0%, P < .001), SDS (MD = -2.55, 95% CI [-3.51, -1.58], I2 = 0%, P < .001), OSNC (OR = 3.13, 95% CI [1.59, 6.17], I2 = 23%, P = .001), BCT (MD = -23.43, 95% CI [-25.07, -21.80], I2 = 45%, P < .001), HRCT (MD = -20.08, 95% CI [-21.70, -18.46], I2 = 29%, P < .001), ET (MD = -2.31, 95% CI [-2.56, -2.06], I2 = 5%, P < .001), and RDR (MD = -2.11, 95% CI [-2.45, -1.77], I2 = 0%, P < .001). CONCLUSION: MNC may benefit for patients with coronary heart disease undergoing CCTA. Future studies are still needed to warrant the current findings.


Assuntos
Angiografia por Tomografia Computadorizada , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Cuidados de Enfermagem/métodos , Doença das Coronárias/diagnóstico por imagem , Satisfação do Paciente
12.
Front Med (Lausanne) ; 11: 1420012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39131086

RESUMO

This review examines recent advancements in interventional treatments and nursing care for lower extremity deep vein thrombosis (DVT), highlighting significant innovations and their clinical applications. It discusses the transition to novel anticoagulants such as Direct Oral Anticoagulants, which offer a safer profile and simplified management compared to traditional therapies. Mechanical interventions, including balloon angioplasty and venous stenting, are detailed for their roles in improving immediate and long-term vascular function in acute DVT cases. Furthermore, the use of image-guided techniques is presented as essential for enhancing the accuracy and safety of DVT interventions. Additionally, this study outlines advances in nursing care strategies, emphasizing comprehensive preoperative and postoperative evaluations to optimize patient outcomes. These evaluations facilitate tailored treatment plans, crucial for managing the complex needs of DVT patients. Long-term care strategies are also discussed, with a focus on patient education to ensure adherence to treatment protocols and to prevent recurrence. The synthesis aims to inform healthcare professionals about cutting-edge practices in DVT management, promoting a deeper understanding of how these advancements can be integrated into clinical practice. It also underscores the necessity for ongoing research to address challenges such as cost-effectiveness and patient compliance, ensuring that future treatments are both accessible and effective.

13.
Front Plant Sci ; 15: 1438215, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39119496

RESUMO

Rice-wheat and maize-wheat rotations are major cropping systems in the middle and lower reaches of Yangtze River in China, where high nitrogen (N) inputs and low N efficiency often exacerbate resource waste and environmental pollution. Due to the changes in factors such as soil properties and moisture content, the N fate and the N utilization characteristics of wheat in different rotations are significantly different. Efficient N management strategies are thus urgently required for promoting maximum wheat yield in different rotation systems while reducing N loss. A 2-year field experiment using isotopic (15N) tracer technique was conducted to evaluate the fate of 15N-labeled urea in wheat fields and the distribution characteristics of N derived from different sources. The wheat yield and N use efficiency under various N rates (180 and 240 kg ha-1, abbreviated as N180 and N240) and preceding crops (rice and maize, abbreviated as R-wheat and M-wheat) were also investigated. The results showed that N240 increased N uptake and grain yield by only 8.77-14.97% and 2.51-4.49% compared with N 180, but decreased N agronomic efficiency (NAE) and N physiological efficiency (NPE) by 14.78-18.79% and 14.06-31.35%. N240 also decreased N recovery in plants by 2.8% on average compared with N180, and increased N residue in soil and N loss to the environment. Compared with that of basal N, the higher proportion of topdressing N was absorbed by wheat rather than lost to the environment. In addition, the accumulation of topdressing N in grain was much higher than that of basal N. Compared with that in R-wheat treatment, plants in M-wheat treatment trended to absorb more 15N and reduce unaccounted N loss, resulting in higher yield potential. Moreover, the M-wheat treatment increased N recovery in 0-20 cm soil but decreased 80-100 cm soil compared with R-wheat treatment, indicating a lower risk of N loss in deeper soil. Collectively, reducing N application rate and increasing the topdressing ratio is an effective way to balance sustainable crop yield for a secure food supply and environmental benefit, which is more urgent in rice-wheat rotation.

14.
Medicine (Baltimore) ; 103(29): e39012, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029031

RESUMO

As a common treatment for rheumatoid arthritis (RA), the adverse reactions of TNF-α inhibitors (TNFis) in practical application have garnered attention. This study aims to investigate the adverse drug events (ADEs) associated with TNFi in RA patients as reported in the FDA Adverse Event Reporting System, to offer insights for clinical use. Cases related to RA and primarily involving TNFi were extracted from the FDA Adverse Event Reporting System database and compared by gender stratification. Screening was conducted based on reporting odds ratio and information component to identify positive ADEs for different TNFis and evaluate common and unique ADEs among various TNFis. There are 4 common ADEs among TNFis, including pulmonary tuberculosis, infection, hypersensitivity, and herpes zoster, as described in the package inserts. However, each TNFi has unique positive ADEs. Adalimumab has 63 unique positive ADEs, including lower respiratory tract inflammation, systemic lupus erythematosus rash, vascular dementia, ovarian neoplasm, adhesion, sarcoma, coccidioidomycosis, etc. Golimumab has 6 unique positive ADEs, including pneumonia cryptococcal, device deployment issue, pneumonia bacterial, polyneuropathy, device malfunction, device issue, etc; certolizumab has 24 unique positive ADEs, including maternal exposure before pregnancy, premature rupture of membranes, exposure via breast milk, staphylococcal sepsis, erysipelas, low birth weight baby, herpes virus infection, premature delivery, etc; etanercept has 180 unique positive ADEs, including joint destruction, chondrolysis, finger deformity, ankle deformity, joint warmth, etc; infliximab has 60 unique positive ADEs, including Hodgkin's disease, metastatic neoplasm, non-Hodgkin's Lymphoma, etc. Although the aforementioned 5 TNFis share common ADEs such as herpes zoster, clinicians must exercise caution when selecting specific medications, especially for RA patients concurrently suffering from malignancies. The analysis indicates that infliximab is associated with 60 unique positive ADEs, including Hodgkin's disease, metastatic neoplasm, and non-Hodgkin's lymphoma; therefore, these patients should use infliximab with greater caution. Similarly, certolizumab should be used with increased caution in pregnant and postpartum women.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Artrite Reumatoide , Fator de Necrose Tumoral alfa , United States Food and Drug Administration , Humanos , Estados Unidos/epidemiologia , Feminino , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Masculino , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antirreumáticos/efeitos adversos , Pessoa de Meia-Idade , Anticorpos Monoclonais/efeitos adversos , Adalimumab/efeitos adversos , Adulto
15.
Expert Opin Drug Saf ; : 1-13, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38753437

RESUMO

BACKGROUND: Ranitidine induced tumor adverse events remains a contradictory clinical question, due to the limited evidence of tumor risk associated with ranitidine in the real world. The purpose of this study was to evaluate the association of ranitidine with all types of tumors through the FAERS database and to provide a reference for clinical use. RESEARCH DESIGN AND METHODS: Cancer cases associated with ranitidine in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023 were extracted to analyze demographic characteristics, and a disproportion analysis was performed. RESULT: A total of 662,998 ranitidine-related cancer cases were screened, and the 50-59 and 60-69 groups accounted for the largest proportion. In PT signal detection, ranitidine was associated with 98 PT, including penal cancer stage II, gastric cancer stage II, et al. In terms of outcome events, adverse events were higher in men (20.65%) than in women (18.47%). CONCLUSIONS: Ranitidine may induce various tumor-related adverse reactions, especially in long-term users and elderly patients. For these patients, tumor screening should be strengthened, and long-term use of ranitidine should be avoided. Since this study cannot prove causality, further evidence is needed for prospective studies with a larger sample size.

16.
Mol Neurobiol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954252

RESUMO

Spinal cord injury (SCI) is a severe traumatic condition in spinal surgery characterized by nerve damage in and below the injured area. Despite advancements in understanding the pathophysiology of SCI, effective clinical treatments remain elusive. Selenium compounds have become a research hotspot due to their diverse medicinal activities. Previously, our group synthesized a selenium-containing Compound 34# with significant anti-inflammatory activity. This study aimed to explore the anti-SCI effects of selenium-containing compounds using network pharmacology, molecular docking (MD), and ADMET methods. To identify SCI-related targets and those associated with 34#, GeneCards, NCBI, and SEA databases were employed. Eight overlapping targets were considered candidate targets, and molecular docking was performed using the PDB database and AutoDock software. The STRING database was used to obtain protein-protein interactions (PPI). Molecular dynamics simulation, MM/GBSA binding free energy score, and ADMET prediction were used to evaluate the potential targets and drug properties of 34#. Finally, experiments on NSC34 cells and mice were to verify the effects of 34# on SCI. Our results revealed eight candidate targets for 34# in the treatment of SCI. PPI and MD identified ADRB2 and HTR1F as the highest connectivity with 34#. ADMET analysis confirmed the low toxicity and safety of 34#. In vitro and in vivo models validated the anti-SCI effects. Our study elucidated candidate targets for alleviating SCI with 34#, explored PPI and target-related signaling pathways, and validated its anti-SCI effects. These findings enhance our understanding of 34#'s mechanism in treating SCI, positioning it as a potential candidate for SCI prevention.

17.
J Am Chem Soc ; 135(32): 11708-11, 2013 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-23899287

RESUMO

To better understand the structural origins of inhibitor selectivity of human phosphodieasterase families (PDEs 1-11), here we report the X-ray crystal structure of PDE2 in complex with a highly selective, nanomolar inhibitor (BAY60-7550) at 1.9 Å resolution, and the structure of apo PDE2 at 2.0 Å resolution. The crystal structures reveal that the inhibitor binds to the PDE2 active site by using not only the conserved glutamine-switch mechanism for substrate binding, but also a binding-induced, hydrophobic pocket that was not reported previously. In silico affinity profiling by molecular docking indicates that the inhibitor binding to this pocket contributes significantly to the binding affinity and thereby improves the inhibitor selectivity for PDE2. Our results highlight a structure-based design strategy that exploits the potential binding-induced pockets to achieve higher selectivity in the PDE inhibitor development.


Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/química , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Imidazóis/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Triazinas/farmacologia , Sítios de Ligação , Cristalografia por Raios X , Humanos , Imidazóis/química , Simulação de Acoplamento Molecular , Inibidores de Fosfodiesterase/química , Ligação Proteica , Triazinas/química
18.
Drug Dev Ind Pharm ; 39(11): 1712-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23062067

RESUMO

Characterization and antitumor activity of basic fibroblast growth factor-mediated active targeting doxorubicin microbubbles (bFGF-DOX-MB) were investigated. Pluronic F68 with chemical conjugation of doxorubicin (DOX-P) and peptide KRTGQYKLC-conjugated DSPE-PEG2000 were prepared. bFGF-DOX-MB had a normal distribution of particle size, with average particle size of 2.7 µm. Using A549 mouse model, bFGF-DOX-MB combined ultrasound showed the best inhibition effect on tumor volume growth among all the test groups. Similar conclusion was obtained from experimental measurements of tumor weight change and blood cell count. From the results, chemotherapeutic drug inhibition on tumor growth could be enhanced by local ultrasound combined with active targeting bFGF-DOX-MB, which might provide a potential application for ultrasound-mediated chemotherapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Microbolhas/uso terapêutico , Oligopeptídeos/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Animais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/efeitos adversos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/efeitos adversos , Estudos de Viabilidade , Fator 2 de Crescimento de Fibroblastos/efeitos adversos , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Microbolhas/efeitos adversos , Proteínas de Neoplasias/metabolismo , Oligopeptídeos/efeitos adversos , Oligopeptídeos/química , Oligopeptídeos/uso terapêutico , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/uso terapêutico , Domínios e Motivos de Interação entre Proteínas , Distribuição Aleatória , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Drug Dev Ind Pharm ; 38(9): 1090-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22188116

RESUMO

Experiments in vitro and in vivo were designed to investigate tumor growth inhibition of chemotherapeutics-loaded liposomes enhanced by acoustic cavitation. Doxorubicin-loaded liposomes (DOX liposomes) were used in experiments to investigate acoustic cavitation mediated effects on cell viability and chemotherapeutic function. The influence of lingering sensitive period after acoustic cavitation on tumor inhibition was also investigated. Animal experiment was carried out to verify the practicability of this technique in vivo. From experiment results, blank phospholipid-based microbubbles (PBM) combined with ultrasound (US) at intensity below 0.3 W/cm² could produce acoustic cavitation which maintained cell viability at high level. Compared with DOX solution, DOX liposomes combined with acoustic cavitation exerted effective tumor inhibition in vitro and in vivo. The lingering sensitive period after acoustic cavitation could also enhance the susceptibility of tumor to chemotherapeutic drugs. DOX liposomes could also exert certain tumor inhibition under preliminary acoustic cavitation. Acoustic cavitation could enhance the absorption efficiency of DOX liposomes, which could be used to reduce DOX adverse effect on normal organs in clinical chemotherapy.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Veículos Farmacêuticos/química , Terapia por Ultrassom/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Transporte Biológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Doxorrubicina/administração & dosagem , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Lecitinas/química , Lipossomos , Masculino , Camundongos , Camundongos Nus , Microbolhas , Sonicação , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Phys Chem Lett ; 13(12): 2718-2724, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35311293

RESUMO

First-principles quantum dynamics calculations show that charge carrier lifetimes, charge transport, and lattice stability are notably improved when BA (CH3(CH2)3NH3+) in BA2PbI4 is replaced with MTEA (CH3(CH2)2SNH3+). By suppressing atomic fluctuations, MTEA enhances the lattice stiffness and inhibits loss of coherence due to the S-S interaction. By delocalizing hole wave functions on the MTEA, particularly on the S atoms, while maintaining the electron wave functions largely unchanged compared to the BA2PbI4, MTEA serves to enhance charge transport and NA coupling while narrowing the bandgap by 0.18 eV. Overall, MTEA decreases NA coupling due to slow atomic motions against a large overlap of electron-hole wave functions, which suppresses nonradiative electron-hole recombination and prolongs carrier lifetime twice longer compared with BA2PbI4. This simulation presents a rational route to make high performance two-dimensional perovskite solar cells.

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